The purpose of this project is to use genetic tools to analyse the biochemical elements which are responsible for the control of cyclic nucleotide levels in eucaryotic cells, and to analyse the response of those cells to changes in cyclic nucleotide levels, or in related enzymes, in an intact developing, higher organism. Chromomere 3D4 of the polytene chromosomes of Drosophila melanogaster has been found to control the level of cAMP phosphodiesterase activity in flies and to affect male spermatogenesis and female oogenesis. The biochemical and physiological consequences of mutations in 3D4 will be investigated. Means will be explored to extend genetic analysis to other elements of the cyclic nucleotide system such as adenylate and guanylate cyclases, cGMP phosphodiesterase and cAMP-binding proteins. In vivo relationships between cAMP metabolism and cGMP metabolism will be explored by genetic means. Genetic techniques will be used to experimentally control the levels of cyclic nucleotides, or related enzymes, in specific cells and at specific stages of development of Drosophila in order to determine the developmental and physiological roles of these molecules in the intact organism.